CN114585259A - Composition containing A2-beta-casein for promoting improvement of character in young mammals - Google Patents

Composition containing A2-beta-casein for promoting improvement of character in young mammals Download PDF

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CN114585259A
CN114585259A CN202080073543.XA CN202080073543A CN114585259A CN 114585259 A CN114585259 A CN 114585259A CN 202080073543 A CN202080073543 A CN 202080073543A CN 114585259 A CN114585259 A CN 114585259A
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nutritional composition
casein
beta
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milk
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陈亦谱
D·J·格拉思沃尔
姚漫江
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Societe des Produits Nestle SA
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/18—Peptides; Protein hydrolysates
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/20—Reducing nutritive value; Dietetic products with reduced nutritive value
    • A23L33/21—Addition of substantially indigestible substances, e.g. dietary fibres
    • A—HUMAN NECESSITIES
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    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
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    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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    • A23V2400/11—Lactobacillus
    • A23V2400/165—Paracasei
    • A—HUMAN NECESSITIES
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    • A23V2400/11—Lactobacillus
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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    • A23V2400/00—Lactic or propionic acid bacteria
    • A23V2400/51—Bifidobacterium
    • A—HUMAN NECESSITIES
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    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2400/00—Lactic or propionic acid bacteria
    • A23V2400/51—Bifidobacterium
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2400/00—Lactic or propionic acid bacteria
    • A23V2400/51—Bifidobacterium
    • A23V2400/519—Breve
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2400/00—Lactic or propionic acid bacteria
    • A23V2400/51—Bifidobacterium
    • A23V2400/533—Longum

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Abstract

The present invention relates to nutritional compositions for improving the character of young children. This nutritional combination for infants or toddlers comprises a 2-beta-casein, wherein the a 2-beta-casein represents more than 50%, preferably more than 70%, more preferably more than 90%, even more preferably 95% or most preferably 100% of the total beta-casein. The composition has been clinically proven to improve the character of toddlers and young children.

Description

Composition containing A2-beta-casein for promoting improved character in young mammals
Technical Field
The present invention relates to a nutritional composition comprising Growing Up Milk (GUM) containing a greater amount of a 2-beta-casein than a 1-beta-casein for promoting an improvement in the character of a young mammal.
Background
It is of paramount importance to provide the most appropriate nutritional support for young mammals, especially at the earliest stages of life.
Nutrition given to young mammals is known to affect many physiological parameters, including not only growth and development, but also digestive comfort, response to allergens later in life and shortly thereafter, and some degree of cognitive function. Today, certain food ingredients are associated with irritability and feelings of depression in young children. These food ingredients are usually of the artificial colour, sugar (in the form of sucrose and glucose), some preservatives and, of course, food allergens. However, even with these ingredients avoided, some infants are still prone to irritability, poor sociability, and more difficult to sooth when they are distracted. These children may be considered "bad" globally. "poorly behaved" may be defined as an easy dysphoria, poor sociability, and poor pacification.
For example, "poor performance" in young children, including toddlers and young children, may initially lead to poor interaction between the child and a responsible caregiver, such as a parent, and subsequently lead to poor relationships. This not only in the short term, but also in the future may cause serious emotional problems for the child, for example, due to lack of confidence.
Given that soothing or improving a baby's poor performance may have a potential long-term impact on his (and his immediate accompanying) person later in life, it is important to provide solutions for improving the poor performance of babies, especially infants and toddlers.
Importantly, the toddlers and their caregivers may enjoy the toddlers' ability to socialize, placate (i.e., self-placate or placate by the caretaker), little, and short periods of irritability.
There is a need to provide solutions that can improve the character of young children, in particular toddlers and young children under six years of age.
There is a need to provide solutions that allow young mammals, in particular toddlers and young children, to self-soothe or be soothed by caregivers.
There is a need to provide solutions that promote sociability in young mammals, particularly toddlers and young children.
There is a need to provide solutions that reduce the frequency and intensity of irritative episodes in young mammals, particularly toddlers and young children.
The inventors have found that a specific mammalian milk component, the a2 variant of beta-casein, may provide the above described effects. A1 and a2 β -casein are genetic variants of β -casein milk protein, which differ by one amino acid.
Thus, "milk a 2" generally refers to various bovine milks that are predominantly deficient in a form of beta-casein called a1 and predominantly have the form a 2. A2 bovine Milk is commercially available from a2 Milk Company (Auckland, New Zealand). Non-bovine milk, including human, sheep, goat, donkey, yak, camel, buffalo, etc., also contains primarily a2 β -casein, so the term "a 2 milk" is also used in this context.
The inventors have clinically demonstrated that milk a2 and a milk a 2-derived products comprising a2- β -casein unexpectedly provide a character improving effect in young children independent of intestinal comfort. In particular, the effect of a2 milk-derived nutritional composition is observed, wherein a 2-beta-casein represents more than 50%, preferably more than 70%, more preferably more than 90%, even more preferably 95% or most preferably 100% of the total beta-casein.
Disclosure of Invention
It is an object of the present invention to provide nutritional compositions comprising e.g. infant formula or growing-up milk (GUM) which may improve the character of young mammals, in particular human infants, toddlers or young children.
Accordingly, one aspect of the present invention relates to a nutritional composition for infants or toddlers comprising a2- β -casein, wherein the a2- β -casein comprises more than 50%, preferably more than 70%, more preferably more than 90%, even more preferably 95% or most preferably 100% of the total β -casein, for improving the character of young mammals, in particular toddlers and young children.
According to one embodiment of the invention, the beta-casein is derived with reduced beta-casein
Figure BDA0003605226630000031
The fraction of whey protein with peptone content is provided in the form of a fraction of whey protein with peptone content.
According to one embodiment of the invention, the pulse peptone content is at most 9 wt.%, based on total protein in the nutritional composition.
According to one embodiment of the invention, the
Figure BDA0003605226630000032
The peptone is PP8 fast, PP8 slow and/or PP-5A.
According to one embodiment of the invention, the nutritional composition may be used for reducing the irritability of infants, toddlers or young children.
According to one embodiment of the invention, the nutritional composition may be used to improve the ability of an infant, toddler or young child to self-soothe or be soothed by a caregiver.
According to one embodiment of the invention, the nutritional composition may be used to improve sociability of an infant, a toddler or a toddler.
According to one embodiment of the invention, the nutritional composition further comprises one or more prebiotics.
According to one embodiment of the invention, the nutritional composition further comprises one or more probiotics.
According to one embodiment of the invention, the a2- β -casein is SEQ ID no 1.
Drawings
Fig. 1 shows a schematic regulatory analysis of the effect of a2GUM on intestinal comfort and personality. Regulatory analysis showed that the effects of a2GUM on character were not affected by the gut comfort variable (p ═ 0.51).
FIG. 1A: c is the total impact of a2 on character, including the possible residual impact of improved bowel comfort.
FIG. 1B: c' (ADE) is the direct effect of a2 on character. ACME is a tuning variable to assess whether the effect of a2 on personality is affected by gut comfort.
Detailed Description
Definition of
Before discussing the present invention in further detail, the following terms and conventions are first defined.
The term "a 2 β -casein" refers to a protein having an amino acid sequence according to SEQ ID NO: 1, a2 variant of bovine beta-casein (secreted form of the protein). In the context of the present invention, other variants comprising a proline at position 67 may be included in a2 β -casein.
The term "a 1 β -casein" refers to a protein having an amino acid sequence according to SEQ ID NO: 2 (a) a1 variant of bovine beta-casein (secreted form of the protein). SEQ ID NO: 1 and SEQ ID NO: 2 differ only in that: a1 β -casein contains histidine at position 67, whereas a2 β -casein contains proline at position 67. In the context of the present invention, other variants comprising histidine at position 67 may be included in a1 β -casein.
The term "intact beta-casein" refers to a protein that is not cleaved except for removal of a signal sequence, e.g. as defined by SEQ ID NO: 1 and SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof.
The term "WPC" refers to "whey protein concentrate". In the context, WPC includes traditional WPC as defined according to USP as well as lactose reduced whey and mineral reduced whey, i.e. protein levels can be as low as 10% w/w.
The term "WPI" refers to "whey protein isolate" and is a whey protein concentrate having a whey protein content of not less than 90% by weight on a dry basis.
The term "whey protein fraction" refers to a composition comprising whey proteins (e.g., WPC and/or WPI).
The term "standard SMP" refers to "standard skimmed milk powder" and is derived from milk obtained from a mixed dairy herd and thus comprises a number of variants of beta-casein, including a1 beta-casein and a2 beta-casein.
The term "a 2 SMP" refers to "a 2 skim milk powder" and contains only a2 β -casein and no a1 β -casein.
The term "proteinaceous form" refers to a highly related protein molecule produced by all sources of combinatorial variation that result in the production of products from a single gene. This includes products that differ by genetic variation, or by spliced RNA transcripts and post-translational modifications.
Term
Figure BDA0003605226630000041
Peptone "with that used by Swaisgood 1982
Figure BDA0003605226630000042
Peptone is the same, i.e., the term
Figure BDA0003605226630000043
Peptone "refers to those proteins/peptides that remain in solution after heating cow's milk at 95 ℃ for 20 minutes, and then acidifying the milk to pH 4.7 with 12% trichloroacetic acid.
The term "beta-casein derived
Figure BDA0003605226630000044
Peptone "means that it is derived from casein only
Figure BDA0003605226630000045
Peptones, such as PP-5, PP-8 fast and PP-8 slow.
Term
Figure BDA0003605226630000051
Peptone 5 "," PP5 "or" PP-5 "refers to beta-casein derived residues 1-105 and 1-107.
Term
Figure BDA0003605226630000052
Peptone 8 fast "," PP8f "or" PP8 fast "refer to beta-casein derived residues 1-28. PP8 is also referred to as "bcas 4P 1-28".
Term
Figure BDA0003605226630000053
Peptone 8 slow "," PP8s "or" PP8 slow "refer to beta-casein derived residues 29-105 and 29-107. PP8 is also referred to as "bcas 1P 29-105" and "bcas 1P 29-107".
The term "infant" generally refers to children under the age of 12 months; in one embodiment, the meaning of the term may be extended to include children of any age of 18 months and below, or to include children of any age of 24 months and below.
The term "toddler" generally refers to a child of from the age at which walking begins to reach about 36 months of age.
The term "young child" refers to a child aged 12 months to 6 years.
As used in this specification, the terms "comprises," "comprising," and the like, are not to be construed in an exclusive or exhaustive sense. In other words, these words are intended to mean "including, but not limited to".
As used herein, the term "nutritional composition" includes, but is not limited to, complete nutritional compositions, partial or incomplete nutritional compositions, nutritional supplements, and nutritional compositions specific to a disease or condition.
As used herein, the term "nutritional supplement" or "dietary supplement" refers to a nutritional product that provides an individual with nutrients that the individual may not otherwise consume in sufficient quantities.
As used herein, the term "food product" refers to any kind of product that is safe for human or animal consumption. The food product may be in solid, semi-solid, or liquid form and may comprise one or more nutrients, foods, or nutritional supplements. For example, the food product may additionally comprise the following nutrients and micronutrients: a protein source, a lipid source, a carbohydrate source, vitamins and minerals. The composition may also contain antioxidants, stabilizers (when provided in solid form) or emulsifiers (when provided in liquid form).
As used herein, the term "infant formula" refers to compositions that are administered to infants and toddlers in place of or in addition to human milk. Infant formulas (also known as "formulas") are defined by the U.S. federal Food, Drug, and Cosmetic Act (FFDCA) as "foods intended to be used as or only for special diets as a result of mimicking the applicability of human milk or as a complete or partial replacement for human milk" Food intended for infant Food. It is also defined by european regulations (directive on the committee for infant and follow-up infant formulas on 14.5.1991 (91/32I/EEC)) and by the guidelines issued by the committee of food law "standard for infant and follow-up infant formula for specific medical purposes" CODEX STAN 72-1981(2015 edition), "standard for infant and follow-up infant formula for specific medical purposes" adopted as a global standard in 1981, revised 1983, 1985, 1987, 2011 and 2015, revised 2007).
Infant formulas may contain, for example, bovine milk whey protein and casein as a protein source, a blend of vegetable oils as a fat source, lactose as a carbohydrate source, vitamin and mineral mixtures, and other ingredients, depending on the manufacturer. Infant formulas for infants allergic to other bovine milk proteins may contain soy as a protein source in place of bovine milk, or may contain partially or extensively hydrolyzed bovine milk proteins. Infant formulas may also be based on sheep milk, goat milk, camel milk or buffalo milk. Infant formulas may be specifically formulated to meet the nutritional needs of the infant within the first six months after birth (formula 1) or after six months (follow-up infant formula). Premature or low birth weight infants IF can also be used in premature or low birth weight infants.
The term "growing up milk" or "GUM" refers to milk (usually cow milk) that has been fortified with iron or other minerals and vitamins; it is generally intended for administration to infants over 12 months until they reach about 36 months.
The term "nutritional composition" refers to a composition that provides nutrients to an individual. The nutritional composition is typically ingested orally or intravenously. It may comprise a lipid or fat source, a carbohydrate source and/or a protein source. The nutritional compositions of the present invention may be in solid form (e.g., powder) or liquid form.
In a particular embodiment, the composition of the invention is a hypoallergenic nutritional composition. The expression "hypoallergenic nutritional composition" refers to a nutritional composition which is less likely to cause allergy.
In a specific embodiment, the nutritional composition of the invention is a "synthetic nutritional composition". The expression "synthetic nutritional composition" refers to a chemically and/or biologically obtained mixture, which may be chemically identical to the mixture naturally occurring in mammalian milk (i.e., the synthetic nutritional composition is not breast milk).
"probiotic" refers to a microbial cell preparation or microbial cell composition that has a beneficial effect on the health or wellness of the host. The definition of probiotic bacteria was given by Salminen S et al in 1999.
"prebiotic" refers to a selective fermentation ingredient that allows for the specific alteration of the activity of the composition and/or the gastrointestinal microbiota that provides a benefit to the health of the host. Prebiotics were discussed in Roberfroid MB, 2007.
Protein fraction comprising a 2-beta-casein
The nutritional compositions of the invention may typically comprise a protein source in an amount of no more than 4.0, 3.0 or 2.1g/100kcal, preferably 1.8 to 2.1g/100 kcal.
It is generally preferred that more than 50% by weight of the protein source is whey.
In one embodiment, the protein content is between 30% and 80% whey protein. Thus, protein sources based on whey, casein and mixtures thereof may be used, as may protein sources based on soy.
For whey proteins of interest, the protein source may be based on acid whey or sweet whey or mixtures thereof, and may contain alpha-lactalbumin and beta-lactoglobulin in any desired proportions.
In one embodiment of the invention the nutritional composition comprises proteins which are a mixture of whey proteins and casein proteins, wherein the ratio of whey proteins to casein proteins is between 50: 50 and 80: 20, preferably 60: 40.
For casein, the al/a2 β -casein ratio is usually important. In particular, a 2-beta-casein (SEQ ID NO 1) represents more than 50%, preferably more than 70%, more preferably more than 90%, even more preferably 95% or most preferably 100% of the total beta-casein present in the composition.
According to one embodiment of the invention a 2-beta casein represents more than 50% of the total beta casein. According to one embodiment of the invention a 2-beta-casein represents more than 70% of the total beta-casein. According to one embodiment of the invention, the a 2-beta-casein represents more than 80% of the total beta-casein. According to one embodiment of the invention a 2-beta casein represents more than 90% of the total p-casein. According to one embodiment of the invention a 2-beta-casein represents more than 95% of the total beta-casein. According to one embodiment of the invention, the a 2-beta-casein is 100% of the total beta-casein. In this case, a1- β -casein (SEQ ID no 1) is not present in the composition.
Generally, the protein can be an intact protein or a hydrolyzed protein, or a mixture of intact and hydrolyzed proteins. It may be desirable to supply partially hydrolysed proteins (degree of hydrolysis between 2% and 20%), for example for infants deemed to be at risk of developing milk allergy. If hydrolyzed proteins are used, the hydrolysis process can be carried out as desired and as is known in the art. For example, whey protein hydrolysates may be prepared by enzymatic hydrolysis of whey fractions in one or more steps. If the whey fraction used as starting material is substantially free of lactose, it is found that the protein undergoes much less lysine blocking during the hydrolysis process. This enables the degree of lysine blockage to be reduced from about 15 wt% total lysine to less than about 10 wt% lysine; for example about 7 wt% lysine, which greatly improves the nutritional quality of the protein source.
According to one embodiment of the invention, the nutritional composition may comprise a composition having reduced beta-casein derivatization
Figure BDA0003605226630000081
Whey protein fraction of peptone content. Due to standard production methods, the available whey protein fractions for formulating nutritional compositions (including infant formulas and growing up milk) typically comprise A1 whey and/or A1a2 whey. However, this has not previously been considered a problem (e.g. for the production of a2 infant formula) since a1 β -casein will precipitate during whey preparation and will not be part of the whey protein fraction. However, it has been shown in EP application No. 18214628.2 that a1 beta-casein derived protein is detected in whey protein fractions such as WPC
Figure BDA0003605226630000082
Peptone.
Thus, advantageously, the nutritional composition may comprise a protein with reduced beta-casein derivatization
Figure BDA0003605226630000083
Whey protein fraction of peptone content. Such a whey protein fraction may be provided by a method comprising the steps of:
(i) providing a whey protein fraction;
(ii) determining and quantifying the beta-casein derived in the whey protein fraction as described herein
Figure BDA0003605226630000084
Peptone; and
(iii) selecting a protein having up to 10% by weight of beta-casein derived based on total protein in the whey protein fraction
Figure BDA0003605226630000085
Said whey protein fraction of peptones, thereby forming a selected whey protein fraction.
A method for performing these steps is described in EP application No. 18214628.2.
According to these methods, beta-casein-derived can be easily detected and quantified
Figure BDA0003605226630000086
Content of peptones (including beta-casein variants and protein forms). Thus, the whey protein fraction can be separated to contain varying amounts of whey protein
Figure BDA0003605226630000087
Whey protein fraction of peptone. Thus, it may be selected to contain up to 10% by weight of the total amount of protein in the whey protein fraction
Figure BDA0003605226630000088
Protein fraction of peptone.
In one embodiment, the selected whey protein fraction is beta-casein derived based on the total protein in the whey protein fraction
Figure BDA0003605226630000089
Beta-casein derived with a peptone content such as up to 9.5 wt. -%
Figure BDA00036052266300000810
Peptones, such as at most 9 wt.%, preferably at most 8.5 wt.%, such as at most 8 wt.%, more preferably at most 7.5 wt.%, such as at most 7 wt.%, even more preferably at most 6.5 wt.%Such as at most 6 wt%, still more preferably at most 5.5 wt%, such as at most 5 wt%, most preferably at most 4.5 wt%, such as at most 4 wt%, at most 3.5 wt%, such as at most 3 wt%, preferably at most 2.5 wt%, such as at most 2 wt%, more preferably at most 1.5 wt%, such as at most 1 wt%, even more preferably at most 0.75 wt%, such as at most 0.50 wt%, still more preferably at most 0.25 wt%, such as at most 0.10 wt%, most preferably at most 0.05 wt%, such as at most 0.01 wt%.
Preferably, the total amount of protein in the whey protein fraction is measured using the Kjeldahl analysis method (ISO 8968-1: 2014).
In one embodiment of the process of the present invention,
Figure BDA0003605226630000092
the peptones are PP8 fast, PP8 slow and/or PP-5. In a further embodiment of the process of the present invention,
Figure BDA0003605226630000093
the peptone is PP8 slow and/or PP-5.
In one embodiment, the whey protein fraction selected has a slow PP8 and/or a PP-5 content of at most 9.5 wt%, such as at most 9 wt%, preferably at most 8.5 wt%, such as at most 8 wt%, more preferably at most 7.5 wt%, such as at most 7 wt%, even more preferably at most 6.5 wt%, such as at most 6 wt%, yet more preferably at most 5.5 wt%, such as at most 5 wt%, most preferably at most 4.5 wt%, such as at most 4 wt%, at most 3.5 wt%, such as at most 3 wt%, preferably at most 2.5 wt%, such as at most 2 wt%, more preferably at most 1.5 wt%, such as at most 1 wt%, even more preferably at most 0.75 wt%, such as at most 0.50 wt%, still more preferably at most 0.25 wt.%, such as at most 0.10 wt.%, most preferably at most 0.05 wt.%, such as at most 0.01 wt.%.
In yet another embodiment of the present invention,
Figure BDA0003605226630000094
the peptone is PP-5.
The nutritional compositions of the present invention may be intended for use in any mammal, such as, for example, humans and pets (such as cats and dogs). In a preferred embodiment, the mammal is a human. In a preferred embodiment, the human is an infant older than 12 months and younger than 6 years of age.
Examples of nutritional compositions are infant formulas, growing-up milk and dairy products suitable for young children.
In one embodiment, the nutritional composition is a follow-on formula for infants over 12 months of age.
In one embodiment, the nutritional composition is a Growing Up Milk (GUM).
Many dairy products containing a 2-beta-casein are currently commercially available and they may be suitable for use in accordance with embodiments of the present invention. For example, reference may be made to "Illuma Atwo 3 paragraph" available from WYETH (USA). The nutritional composition of this product is given in example 2 below. Another example of a commercially available Milk product containing a 2-beta-casein is a2 available from A2 Milk company (Auckland New Zealand)
Figure BDA0003605226630000091
A milk beverage for toddlers. The nutritional composition of this product is given in example 3 below. Another example of a commercially available milk product containing a 2-beta-casein is "Illuma Atwo 2", available from WYETH (USA). The nutritional composition of this product is given in example 4 below.
The general composition of the nutritional composition (such as an infant formula) for use according to the invention may optionally comprise substances which may have a beneficial effect, such as probiotics, fibres, lactoferrin, nucleotides, nucleosides and/or other substances, which are present in the nutritional composition to be fed to the infant in conventional amounts.
The probiotic bacteria may be selected from lactobacilli, such as lactobacillus rhamnosus, lactobacillus paracasei and lactobacillus reuteri, and bifidobacteria, such as bifidobacterium lactis, bifidobacterium breve and bifidobacterium longum.
The nutritional composition (such as a follow-up formula or growing-up milk) may optionally further comprise prebiotics, such as non-digestible carbohydrates that promote the growth of intestinal probiotics.
In a preferred embodiment, the nutritional composition, such as a follow-up formula or a growing-up milk, comprises prebiotics selected from the group consisting of Fructooligosaccharides (FOS), leford fructooligosaccharides, inulin, leford inulin, lactulose, bovine milk oligosaccharides (CMOS) and Galactooligosaccharides (GOS), human milk oligosaccharides (CMOS).
The nutritional composition may also contain all vitamins and minerals that are considered essential to the daily diet, which are present in the composition in nutritionally significant amounts.
Thus, a preferred embodiment relates to a nutritional composition, such as a follow-up formula or Growing Up Milk (GUM), further comprising vitamins.
The minimum requirements for certain vitamins and minerals have been determined. Examples of minerals, vitamins and other nutrients optionally present in the nutritional composition include vitamin a, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin E, vitamin K, vitamin C, vitamin D, folic acid, inositol, niacin, biotin, pantothenic acid, choline, calcium, phosphorus, iodine, iron, magnesium, copper, zinc, manganese, chlorine, potassium, sodium, selenium, chromium, molybdenum, taurine and l-carnitine. The minerals are typically added in salt form.
If necessary, the nutritional composition (such as a follow-on formula or a GUM) may comprise emulsifiers and stabilisers such as soy, lecithin, citric acid mono-and diglycerides and the like. This is especially true if the composition is provided in liquid form.
Another preferred embodiment relates to a nutritional composition, such as a follow-on formula or a GUM, further comprising anhydrous milk fat.
Another preferred embodiment relates to a nutritional composition, such as a follow-on formula or a GUM, further comprising LC-PUFA. Examples of LC-PUFAs that can be added are docosahexaenoic acid (DHA), arachidonic acid (ARA) and EPA. The LC-PUFA may be added at a concentration such that it comprises more than 0.01% of the total FA present in the composition. Thus, the LC-PUFA containing oil may be present in an amount of about 0.2% to 2% by weight of the total lipid in the composition, such as DHA, EPA, DPA and/or ARA.
Probiotics：
In a preferred embodiment, probiotics are comprised in the nutritional composition of the invention. Examples of known probiotic compounds are Bacillus (Bacillus), Bifidobacterium (Bifidobacterium), Bifidobacterium (Lactobacillus), Lactococcus (Lactococcus), Enterococcus (Enterococcus), yeast (Saccharomyces), Kluyveromyces (Kluyveromyces), Candida (Candida), Streptococcus (Streptococcus), in particular selected from Bifidobacterium bifidum subccore, Bifidobacterium lactis, Bifidobacterium animalis, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium adolescentis, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus paracasei, Lactobacillus salivarius, Lactobacillus lactis (Lactobacillus lactis), Lactobacillus reuteri, Lactobacillus rhamnosus, Lactobacillus johnsonii, Lactobacillus plantarum, Lactococcus lactis, Streptococcus thermophilus, Enterococcus faecium, Saccharomyces cerevisiae, Saccharomyces boulardii and escherichia coli. In particular, probiotic and non-replicating probiotic bacteria, such as Lactobacillus, Bifidobacterium or combinations thereof, for example Lactobacillus johnsonii (Lactobacillus johnsonii), Lactobacillus paracasei (Lactobacillus paracasei), Lactobacillus rhamnosus (Lactobacillus rhamnosus), Bifidobacterium longum (Bifidobacterium longum), Bifidobacterium lactis (Bifidobacterium lactis), Bifidobacterium breve (Bifidobacterium breve) or combinations thereof, and the use of these bacteria.
Carbohydrate compound：
A preferred embodiment relates to a nutritional composition, such as a follow-on formula or a GUM, wherein the at least one carbohydrate source is selected from lactose, corn syrup solids, fructose, glucose, maltodextrin, dried glucose syrup, sucrose, trehalose, galactose, maltose, honey powder, starch, oligosaccharides, loford inulin or loford fructo-oligosaccharide.
Lactose can constitute essentially 100% of the carbohydrate content. Other carbohydrates such as saccharin, maltodextrin and starch may also be added. However, in a preferred embodiment, the nutritional composition of the invention may comprise carbohydrates which are preferably used as prebiotics. For example, the prebiotic is preferably selected from the group consisting of 2 ' fucosyllactose, lactodifucotetraose, 3 fucosyllactose, lacto-N-fucopentaose I, lacto-N-fucopentaose II, lacto-N-fucopentaose III, lacto-N-neotetraose, lacto-N-tetraose, 3 ' sialyllactose, 6 ' sialyllactose, 3 ' sialyllacto-N-tetraose, 6 ' sialyllacto-N-neotetraose, inulin, fructo-oligosaccharide (FOS), short chain fructo-oligosaccharide (short chain FOS), galacto-oligosaccharide (GOS), xylo-oligosaccharide (XOS), gangliosides, partially hydrolyzed guar gum, acacia gum, soybean gum, or mixtures thereof.
The one or more carbohydrates may be present in a daily dose of about 1g to 20g or 1% to 80% or 20% to 60% of the composition. Alternatively, the carbohydrate is present in 10% to 80% of the dry composition, for example, in an amount of 9g/100kcal to 14g/100 kcal.
In a preferred embodiment, the lactose comprises more than 98% of the carbohydrates present in the composition.
In one embodiment, the nutritional composition comprises a mixture of oligosaccharides according to WO2007/090894 (see general teachings, in particular example 1). It can be used in particular in combination with GOS. The base formula may provide an oligosaccharide mixture comprising: 5-70 wt.% of at least one N-acetylated oligosaccharide selected from the group comprising: GalNAc α 1, 3Gal β 1, 4Glc and Gal β 1, 6GalNAc α 1, 3Gal β 1, 4 Glc; 20-90 wt% of at least one neutral oligosaccharide selected from the group comprising: gal β 1, 6Ga1, Gal β 1, 6Gal β 1, 4GlcGal β 1, 6Gal β 1, 6Glc, Gal β 1, 3Glc, Gal β 1, 3Gal β 1, 4Glc, Gal β 1, 6Gal β 1, 4Glc, Gal β 1, 6Gal β 1, 3Gal β 1, 4Glc Gal β 1, 3Gal β 1, 6Gal β 1, 4Glc, and Gal β 1, 3Gal β 1, 4 Glc; and 5-50 wt% of at least one sialylated oligosaccharide selected from the group comprising: NeuAc α 2, 3Gal β 1, 4Glc and NeuAc α 2, 6Gal β 1, 4 Glc.
Other components may be added to the nutritional composition, such as vitamins and minerals.
If necessary, the composition of the present invention may contain emulsifiers and stabilizers such as soybean, lecithin, citric acid monoglyceride and citric acid diglyceride, and the like.
The composition may also contain other substances that may have beneficial effects such as lactoferrin, nucleotides, nucleosides, gangliosides, polyamines, and the like. The nutritional composition may also include a flavoring agent, such as, but not limited to, vanillin.
A particular preferred embodiment relates to a nutritional composition, further comprising fructooligosaccharides, such as loford inulin and/or loford fructooligosaccharides.
The nutritional composition (such as a follow-on formula or a GUM) may be a liquid formula or a powder to be reconstituted prior to use. A preferred embodiment is a powdered follow-up formula.
In a preferred embodiment, the nutritional composition is a liquid composition prepared by reconstituting a powder.
In a preferred embodiment, the nutritional composition is a liquid composition, such as liquid Growing Up Milk (GUM).
The nutritional composition may also contain all vitamins and minerals that are considered essential in the daily diet in nutritionally significant amounts. The minimum requirements for certain vitamins and minerals have been determined. Examples of minerals, vitamins and other nutrients present in the nutritional composition include vitamin a, vitamin B1, vitamin B2, vitamin B6, vitamin E, vitamin K, vitamin C, vitamin D, folic acid, inositol, niacin, biotin, pantothenic acid, choline, calcium, phosphorus, iodine, iron, magnesium, copper, zinc, manganese, chloride, potassium, sodium, selenium, chromium, molybdenum, taurine and l-carnitine. The minerals are usually added in the form of salts.
Preparation of nutritional composition：
The nutritional composition according to the invention may be prepared by any known or other suitable means.
Of course, the protein component is the above-mentioned component comprising a 2-beta-casein, which represents more than 50%, preferably more than 70%, more preferably more than 90%, even more preferably 95% or most preferably 100% of the total beta-casein in the composition.
For example, growing-up milk may be completed by blending together a suitable protein source with a carbohydrate source and a lipid source in suitable proportions. If an emulsifier is used, this stage may be included. Vitamins and minerals may be added at this stage, but may also be added subsequently to avoid thermal degradation. Water (preferably reverse osmosis or deionized water) may then be added and mixed in to form a liquid mixture. The mixing temperature is preferably room temperature, but may be higher. The liquid mixture may then be subjected to a heat treatment to reduce bacterial load. The mixture may then be homogenized.
If it is desired to produce a powdered composition, the homogenised mixture is dried in a suitable drying apparatus, such as a spray drier or freeze drier, and converted to a powder.
The process for preparing infant and toddler formula is based on the concept of: the product must be nutritionally adequate and microbiologically safe to eat. Therefore, a step of eliminating or limiting the growth of microorganisms is crucial to the production process. The processing techniques for each particular formula are proprietary to the manufacturer, but generally involve preserving an oil-in-water (o/w) emulsion by dehydration in the case of a powder product, or sterilization in the case of a ready-to-eat or concentrated liquid product. Powdered infant formulas may be produced by various methods, such as dry blending dehydrated ingredients to make a homogeneous formula, or hydrating and wet mixing a mixture of major ingredients (such as fat, protein and carbohydrate ingredients), and then evaporating and spray drying the resulting mixture. A combination of the two methods described above may be used, where the base powder is first prepared by wet mixing and spray drying all or some of the major ingredients, and then the remaining ingredients (including carbohydrates, minerals and vitamins and other micronutrients) are dry mixed to give the final formula. Liquid formulations are provided in ready-to-eat form or as concentrated liquids which require dilution with water, typically 1: 1. The manufacturing processes for these products are similar to those used to manufacture reconstituted milk.
If it is desired to produce a liquid infant formula, the homogenised mixture is filled into a suitable container, preferably under sterile conditions. However, the liquid composition may also be cooked in a vessel, suitable devices for carrying out such filling and cooking being commercially available.
Nutritional compositions based on a 2-beta-casein or having reduced levels of
Figure BDA0003605226630000141
Treatment of nutritional compositions with peptone content Therapeutic uses
The inventors have shown in clinical trials that young children have an improved performance after eating the nutritional composition according to embodiments of the present invention. Example 1 describes a clinical trial showing the positive effect of the nutritional composition of the invention on the character of young children.
Statistically significant results indicate that the administered nutritional composition based on a 2-beta-casein improved the character of the studied young child compared to the control composition. In particular, administration of a nutritional composition based on a2- β -casein reduced the irritability of young children. It also improves the ability of infants, toddlers or young children to self-placate or be placated by caregivers. The administration of a nutritional composition based on a 2-beta-casein also increases the sociability of young children.
According to a particular embodiment, the infant is between 12 months and 6 years of age.
The clinical trial reported here was intended to eliminate the bias due to the difference in character of the group. The randomized design of the study controlled the potential bias from differences in character between the two groups. Subjects were randomly selected to participate in the a2GUM or non-a 2 group. Any character distribution between random groups should be similar. Thus, the effects seen can be attributed to differences in the composition of the applied GUM compositions.
Children receiving the a2 milk product showed significantly better performance compared to children receiving the standard a1/a2 GUM.
The data was analysed to determine whether the positive effect on character observed in young children was due to the fact that the a2- β -casein based GUM might induce any potential increased intestinal comfort compared to a control composition containing a1/a2- β -casein. The reduced irritability shows a schematic diagram, indicating that the personality effect is not related to the intestinal comfort effect.
Thus, the positive effect on character observed by the applicant is independent and distinct from any potential intestinal comfort effect.
Application cycle
The administration period of the nutritional composition of the invention may be continuous or discontinuous. Continuous administration is preferred for more sustained efficacy. Generally, the nutritional composition may be administered at least twice daily, preferably three times daily.
However, it is speculated that a discontinuous pattern (e.g., three administrations per day every other day) may still have a positive effect on the young mammal.
Generally, while positive effects are expected where the duration of administration is relatively short (e.g., daily administration over a period of one to four weeks), it is believed that longer durations provide enhanced effects (e.g., a duration of at least three to six months, preferably at least one year, in humans, and corresponding periods in other mammals).
In one embodiment of the invention, the nutritional composition is intended for consumption by an infant or toddler. In this case, consumption may begin from 12 months and may continue from then on to any age, up to about 36 months.
In one embodiment of the invention, the nutritional composition is intended for consumption by young children. In this case, consumption may begin from three years old, or from 4 years old, or 5 years old, or 6 years old, or from any age, up to about 7 years old.
The invention will now be described in further detail in the following non-limiting examples.
Examples
EXAMPLE 1 clinical study
The primary objective was to compare the overall digestive comfort between a 12-36 month old toddler consuming a GUM containing only a 2-beta-casein (a2 GUM) and a toddler consuming a traditional non-a 2 dairy product over a2 week study period.
Design of research
The study was a multicenter, non-control post-market study with subjects who were infants between 12 and 36 months who met the criteria for study inclusion and exclusion. A total of 387 subjects participated in this trial (259 in the A2GUM group and 128 in the non-A2 GUM group). Subjects were assigned to receive A2GUM (Wyeth Illuma Atwo growing milk, currently commercially available in China, see example 2), control A2GUM (a 2)
Figure BDA0003605226630000151
Toddler milk drink, see example 3), or continued use of non-a 2 milk. Subjects were randomly assigned to each group using an a priori determined assignment schedule. On study day 1, subjects were assigned the assigned study GUM (for the a2GUM or control a2GUM group) or instructed their children to continue the habitual feeding regimen of non-a 2 milk and dairy products (the traditional non-a 2 milk group). Three a2GUM or control a2GUM were dispensed daily and the caregivers were instructed to provide study GUM for 14 days. Subjects and caregivers received 2 outpatient visits on study days 1 and 15 and completed study questionnaires on study days 1, 5-7, and 12-14. The primary outcome measure of the study was a combined intestinal comfort score (GCS) derived from nine baby intestinal comfort questionnaires. The potential range of GCS is 10 to 60, with higher scores indicating higher GI burden. Baseline assessments were derived from a 24-hour session on the previous day, with assessments from study days 7 and 14 being derived from the mean of 3 consecutive days from days 5-7 and 12-14, respectively. Secondary results of the study included 1) ofBody GI symptom/behavior frequency and severity score, 2) stool frequency and stool consistency score, 3) milk intake (type and volume), 4) milk satisfaction score, 5) anthropometry (weight, height, head circumference and corresponding anthropometric Z score), and 6) child personality. In the results section, the a2GUM refers to the combined a2GUM group.
The personality of young children and children was assessed through parental reports using a short version of the infant behavioral questionnaire (ECBQ), which has been validated in multiple studies and used in chinese populations. The questionnaire includes 9 questions covering a plurality of behavioral areas such as fear, depression, impulsion, sociability, pacification, sadness, and shame. Questionnaires were performed on all subjects on study day 14. ANOVA was used to assess the difference in behavioral range between the a2GUM and the non-a 2 milk groups. Afterwards, correlations are also calculated and displayed using a scatter plot matrix between each individual measurement and the individual character measurement in the GCS, and a typical correlation is calculated overall.
Results of the study-character
Table 1: day 14 character questionnaire (FAS)
Figure BDA0003605226630000171
Figure BDA0003605226630000181
FAS is the complete analysis group. Differences in mean character measures at day 14 were analyzed using ANOVA. Of the nine personality questions, the a2GUM and non-a 2 milk groups had 4 significant differences in mean scores at day 14. Compared to the non-a 2 milk group (3 questions, in all cases p < 0.05), the a2GUM group reports an average sociality ("how often do your child find this child accompanying when a familiar child comes to your home?and a peaceful" when a familiar adult (e.g. a relative or friend) visits your home, how often your child wants to interact with an adult?, and a peaceful "score (how often your child becomes easy to peaceful when she/he is distracted), but a lower average activity level (" how often your child runs into the house when playing indoors ") score (p ═ 0.03).
Further data exploration was conducted to investigate whether the effects observed in the character are mediated by positive benefits on intestinal comfort. The gut comfort questionnaire and character are summarized by a principal component score, which is a weighted sum of questionnaire scores, where the weights are selected in a way that maximizes the treatment effect. Fig. 1 shows a schematic diagram of the data analysis results.
Estimating 95％CI p value
ACME -0.019 -0.097，-0.097 0.51
ADE 0.725 0.170，1.276 0.008
Total Effect (c) 0.706 0.158，1.253 0.01
TABLE 2
As shown in table 2, regulatory analysis showed that the effect of a2 on character was not affected by the intestinal comfort variable (p ═ 0.51). In contrast, a2GUM has a direct effect on character and is statistically significant (p ═ 0.008). Furthermore, the effect remained stable when assessing the overall effect of a2 on the character (0.725 versus 0.706), further supporting that the effect of a2 on the character was independent of the effect on gut comfort.
Thus, the improved performance observed after administration of a2GUM may not be described as a side effect of improving intestinal comfort. The effects are different and not relevant.
Example 2
Containing a 2-beta-casein
Figure BDA0003605226630000191
A23 milk powder
Figure BDA0003605226630000192
Figure BDA0003605226630000201
Example 3
Figure BDA0003605226630000202
Toddler milk drink containing a 2-beta-casein was purchased from milk a2 (Auckland, Australia).
Figure BDA0003605226630000203
Figure BDA0003605226630000211
Figure BDA0003605226630000221
Example 4
Containing a 2-beta-casein
Figure BDA0003605226630000222
A22 milk powder
Figure BDA0003605226630000223
Figure BDA0003605226630000231
Sequence listing
SEQ ID NO: 1 (amino acid sequence of A2 beta-casein)：
RELEELNVPG EIVESLSSSE ESITRINKKI EKFQSEEQQQ TEDELQDKIH PFAQTQSLVY PFPGPIPNSL PQNIPPLTQT PVVVPPFLQP EVMGVSKVKE AMAPKHKEMP FPKYPVEPFT ESQSLTLTDV ENLHLPLPLL QSWMHQPHQP LPPTVMFPPQ SVLSLSQSKV LPVPQKAVPY PQRDMPIQAF LLYQEPVLGP VRGPFPIIV
SEQ ID NO: 2(A1 beta-casein amino acid sequence)：
RELEELNVPG EIVESLSSSE ESITRINKKI EKFQSEEQQQ TEDELQDKIH PFAQTQSLVY PFPGPIHNSL PQNIPPLTQT PVVVPPFLQP EVMGVSKVKE AMAPKHKEMP FPKYPVEPFT ESQSLTLTDV ENLHLPLPLL QSWMHQPHQP LPPTVMFPPQ SVLSLSQSKV LPVPQKAVPY PQRDMPIQAF LLYQEPVLGP VRGPFPIIV
Figure IDA0003605226670000011
Figure IDA0003605226670000021
Figure IDA0003605226670000031

Claims (15)

1. Nutritional composition for infants or toddlers comprising a 2-beta-casein, wherein the a 2-beta-casein represents more than 50%, preferably more than 70%, more preferably more than 90%, even more preferably 95% or most preferably 100% of the total beta-casein, for improving the character of young mammals, in particular infants over 12 months old, toddlers and young children.
2. The nutritional composition according to claim 1, wherein the beta-casein is derived with reduced beta-casein
Figure FDA0003605226620000011
The fraction of whey protein with peptone content is provided in the form of a fraction of whey protein with peptone content.
3. The nutritional composition according to claim 1 or 2, wherein the nutritional composition is based on total protein in the nutritional composition
Figure FDA0003605226620000012
The peptone content is at most 9% by weight.
4. A nutritional composition according to claim 2 or 3, wherein the composition is for use as a nutritional supplement
Figure FDA0003605226620000013
The peptone is PP8 fast, PP8 slow and/or PP-5.
5. The nutritional composition according to any one of claims 1 to 4, for use in reducing the irritability of the infant, toddler or young child.
6. The nutritional composition according to any one of claims 1 to 4, for use in improving the ability of the infant, toddler or young child to self-placate or be placated by a caregiver.
7. The nutritional composition according to any one of claims 1 to 4 for use in improving sociability of the infant, toddler or young child.
8. The nutritional composition according to any one of claims 1 to 7, wherein the infant, toddler, or young child suffers from intestinal related pain, constipation, or colic.
9. The nutritional composition according to any one of claims 1 to 7, wherein the infant, toddler, or young child does not have intestinal-related pain, constipation, or colic.
10. The nutritional composition according to any one of claims 1 to 9, wherein the composition further comprises one or more prebiotics.
11. The nutritional composition according to claim 10, wherein the one or more prebiotics are selected from the group consisting of Fructooligosaccharides (FOS), leford fructooligosaccharides, inulin, leford inulin, lactulose, bovine milk oligosaccharides (CMOS) and Galactooligosaccharides (GOS), Human Milk Oligosaccharides (HMOS).
12. The nutritional composition according to any one of claims 1 to 12, wherein the composition further comprises one or more probiotics.
13. The nutritional composition according to claim 7, wherein the one or more probiotics are selected from Lactobacillus rhamnosus, Lactobacillus paracasei and Lactobacillus reuteri, and bifidobacteria, such as Bifidobacterium lactis, Bifidobacterium breve and Bifidobacterium longum.
14. The nutritional composition according to any one of claims 1 to 13, wherein the composition is in the form of a follow-up or a growing-up milk.
15. Nutritional composition according to any of claims 1 to 14, wherein a2- β -casein is SEQ ID no 1.
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116622592A (en) * 2023-07-21 2023-08-22 华南农业大学 Application of buffalo milk in preparation of lactobacillus rhamnosus spray drying protective agent
CN116622592B (en) * 2023-07-21 2023-10-20 华南农业大学 Application of buffalo milk in preparation of lactobacillus rhamnosus spray drying protective agent

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